Generally, the introduction of fluorine atom(s) into an organic molecule can change the physical, chemical properties and biological activity of a compound. Therefore, introduction of fluorine atom(s) into various drugs, macromolecular materials and liquid crystal materials is a commonly used technique for improving the properties of a substance.
1,1-difluorovinyl are an important class of fluorine-containing groups, which are often used in the construction of fluorine-containing skeleton. functional group of 1,1-difluorovinyl can be defluorinated to form monofluoroolefins (Chem. Lett. 1979, 983.), hydrogenated to form difluoromethyl (J. Chem. Soc., Chem. Commun. 1989, 1437.), fluorinated to form trifluoromethyl (J. Org. Chem. 1997, 62, 7758.). The unsaturated double bond can also undergo a nucleophilic addition reaction to form a fluorine-containing heterocyclic ring by intermolecular cycloaddition (Angew. Chem. Int Ed. 2012, 51, 12059.). In addition, functional group of the 1,1-difluorovinyl is considered to be a carbonyl bioisostere in aspect of drug design (J. Chem. Soc., Chem. Commun. 1989, 1437.). The organic molecules containing 1,1-difluorovinyl functional group are often used as enzyme inhibitors (Fluorine in Medicinal Chemistry and Chemical Biology; Wiley-Blackwell: West Sussex, UK, 2009.). Therefore, it is particularly important to simply synthesize organic molecules containing functional group of 1,1-difluorovinyl.
Alkyl borate and alkylboric acid are very important intermediates in the field of organic synthesis (Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine, Wiley-VCH, Weinheim, 2005), which are widely used in the synthesis of various drugs, macromolecular materials, liquid crystal materials and fluorescent probe materials. Compounds containing functional groups of borate or boric acid can be easily converted to corresponding alcohols, aldehydes, amine functional groups (Chem. Commun. 2013, 49, 11230.), in addition to the classical Suzuki-Miyaura coupling (Angew. Chem., Int. Ed. 2011, 50, 6722.). Most compounds containing functional groups of borate or boric acid have good stability compared to other metal organic nucleophilic reagent (such as Grignard reagent), and can be purified or stored directly under air atmosphere, thus it is of great significance to synthesize borate or boric acid compounds with diversiform functional groups.
The difluoroallylboronate compound containing both 1,1-difluorovinyl functional groups and borate functional groups in the molecule is an excellent organic synthetic block, but there is only one case reported about the synthesis of difluoroallylboronate compounds (Angew. Chem. Int. Ed. 2011, 50, 7079), and this method requires a complex carbene copper complex as a catalyst and the yield is low.
3-(4-acetylphenyl)-1-((3r,5r,7r)-adamantine-1-yl)-2,2-difluoro-3-hydroxypropan-1-one (Compound III) is a γ-aminobutyric acid receptor agonist (J. Med. Chem. 2013, 56, 2456). In the existing synthetic route, 1-((3r,5r,7r)-adamantan-1-yl)-4,4,4-trifluoro-3-hydroxy-1-butanone is used as raw material, after fluorination with Selectfluor, detrifluoroacetyl group and addition with aldehydes, it is obtained. The reagent used is relatively expensive (J. Am. Chem. Soc. 2011, 133, 5802).